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Here we present room-temperature spin-dependent charge transport measurements in single-molecule junctions made of metalloporphyrin-based supramolecular assemblies. They display large conductance switching for magnetoresistance in a single-molecule junction. The magnetoresistance depends acutely on the probed electron pathway through the supramolecular wire: those involving the metal center showed marked magnetoresistance effects as opposed to those exclusively involving the porphyrin ring which present nearly complete absence of spin-dependent charge transport. The molecular junction magnetoresistance is highly anisotropic, being observable when the magnetization of the ferromagnetic junction electrode is oriented along the main molecular junction axis, and almost suppressed when it is perpendicular. The key ingredients for the above effect to manifest are the electronic structure of the paramagnetic metalloporphyrin, and the spinterface created at the molecule-electrode contact.
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Objective: Adult growth hormone deficiency (AGHD) patients have an increased cardiovascular morbidity and mortality. Adipsin is an adipokine that is significantly correlated with metabolic disease, especially in people with obesity. The objective of our study was to compare AGHD patients with healthy subjects to evaluate whether adipsin levels are closely related to glycolipid metabolism and cardiovascular risks in AGHD patients. Methods: Our study included 88 AGHD patients and 88 age-, weight-, and body mass index (BMI)-matched healthy subjects. Anthropometric parameters such as BMI, waist circumference, and blood pressure were measured. Biochemical indicators such as serum adipsin, lipids, and fasting insulin levels were determined. Results: Adipsin levels in AGHD patients were significantly increased compared to levels of the control group (11,567.29 ng/mL, interquartile [9,856.46 to 13,360.60 ng/mL]) versus (9,127.86 ng/mL, interquartile [8,061.82 to 10,647.06 ng/mL], P = .000). Increased serum adipsin levels are correlated with cardiovascular risk factors such as a higher waist-to-hip ratio, serum lipids levels, and insulin resistance. Adipsin levels were inversely related to insulin-like growth factor 1 (IGF-1) (r = -0.6363, P<.0001) and insulin-like growth factor binding protein 3 levels (r = -0.498, P<.0001). The odds ratio (OR) for AGHD in the highest quartile was found to be 4.491 times the ratio in the lowest quartile (OR = 4.491, P = .048). Additionally, adipsin was found to be the most independent factor to influence IGF-1 levels in AGHD subjects. Conclusion: The serum levels of adipsin were significantly correlated with glucolipid metabolism disorder with a growth hormone deficiency status. Furthermore, serum levels of adipsin might be a good marker for the occurrence and development of cardiovascular diseases in AGHD patients. Abbreviations: AGHD = adult growth hormone deficiency; ASCVD = atherosclerotic cardiovascular disease; BMI = body mass index; DBP = diastolic blood pressure; FINS = fasting insulin; FPG = fasting plasma glucose; GH = growth hormone; HOMA-IR = homeostatic model to assess insulin resistance index; hsCRP = high-sensitivity C-reactive protein; IGF-1 = insulin-like growth factor 1; IGFBP-3 = insulin-like growth factor binding protein 3; LAP = lipid accumulation products; LDL = low-density lipoprotein; SBP = systolic blood pressure; TC = total cholesterol; TG = triglycerides; WC = waist circumference; WHR = waist-to-hip ratio; OR = odds ratio.
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Enfermedades Cardiovasculares , Adulto , Índice de Masa Corporal , Factor D del Complemento , Hormona del Crecimiento , Humanos , Factores de Riesgo , Circunferencia de la CinturaRESUMEN
A chiral ZnII porphyrin derivative 1 and its achiral analogue 2 were studied in the solid state. Considering the rich molecular recognition of designed metalloporphyrins 1 and 2 and their tendency to crystallize, they were recrystallized from two solvent mixtures (CH2 Cl2 /CH3 OH and CH2 Cl2 /hexane). As a result, four different crystalline arrangements (1 a,b and 2 a,b, from 0D to 2D) were obtained. Solid-state studies were performed on all the species to analyze the role played by chirality, solvent mixtures, and surfaces (mica and HOPG) in the supramolecular arrangements. By means of combinations of solvents and substrates a variety of microsized species was obtained, from vesicles to flower-shaped arrays, including geometrical microcrystals. Overall, the results emphasize the environmental susceptibility of metalloporphyrins and how this feature must be taken into account in their design.
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A chelating coumarin-derived ligand sensitizes all emitting lanthanide ions in the solid state and gives high absolute quantum yields for ethanol solutions of complexes of Sm, Eu, Tb, and Dy, above 20% for the last two. Crystal structures of these four complexes are [Ln(Cum)3(H2O)(X)]·X where X = MeOH or EtOH.
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BACKGROUND: Circular RNAs (circRNAs) play an important role in osteoarthritis (OA). However, the role of circRNA in OA is still unclear. Here, we explored the role and mechanism of circ_0044235 in OA. METHODS: CHON-001 cells were treated with IL-1ß to establish OA model in vitro. The levels of circ_0044235, miR-375 and phosphoinositide 3-kinase (PI3K) regulatory subunit 3 (PIK3R3) were detected by quantitative real-time PCR. Cell count kit-8 assay and flow cytometry assay were used to detect cell viability and apoptosis. The concentrations of inflammation factors were determined by enzyme-linked immunosorbent assay. Western blot was used to detect protein levels. The interaction between miR-375 and circ_0044235 or PIK3R3 was analyzed by dual-luciferase reporter assay and RNA immunoprecipitation assay. RESULTS: Circ_0044235 was significantly decreased in OA cartilage tissue and IL-1ß-treated CHON-001 cells. Overexpression of circ_0044235 promoted IL-1ß-stimulated CHON-001 cell viability and inhibited apoptosis, inflammation, and extracellular matrix (ECM) degradation. In mechanism analysis, circ_0044235 could act as a sponge for miR-375 and positively regulate PIK3R3 expression. In addition, miR-375 ameliorated the effect of circ_0044235 overexpression on IL-1ß-mediated CHON-001 cells injury. In addition, miR-375 inhibition mitigated IL-1ß-induced CHON-001 cell injury, while PIK3R3 silencing restored the effect. CONCLUSION: Circ_0044235 knockdown alleviated IL-1ß-induced chondrocytes injury by regulating miR-375/PIK3R3 axis, confirming that circ_0044235 might be a potential target for OA treatment.
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MicroARNs , Osteoartritis , Humanos , Fosfatidilinositol 3-Quinasas/genética , Osteoartritis/genética , Inflamación , Apoptosis/genética , Condrocitos , Interleucina-1beta/genética , MicroARNs/genéticaRESUMEN
The apolipoprotein ε4 allele ( APOE4 ) is associated with decreased longevity, increased vulnerability to age-related declines, and disorders across multiple systems. Interventions that promote healthspan and lifespan represent a promising strategy to attenuate the development of APOE4 -associated aging phenotypes. Here we studied the ability of the longevity-promoting intervention 17α-estradiol (17αE2) to protect against age-related impairments in APOE4 versus the predominant APOE3 genotype using early middle-aged mice with knock-in of human APOE alleles. Beginning at age 10 months, male APOE3 or APOE4 mice were treated for 20 weeks with 17αE2 or vehicle then compared for indices of aging phenotypes body-wide. Across peripheral and neural measures, APOE4 was associated with poorer outcomes. Notably, 17αE2 treatment improved outcomes in a genotype-dependent manner favoring APOE4 mice. These data demonstrate a positive APOE4 bias in 17αE2-mediated healthspan actions, suggesting that longevity-promoting interventions may be useful in mitigating deleterious age-related risks associated with APOE4 genotype.
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The use of personal media has become increasingly popular in recent years. However, gaining and retaining followers has become increasingly challenging, given the fierce competition among bloggers and the constant changes in personal media. In this context, this study aims to explore the factors that influence followers' continued usage intentions toward personal media bloggers and strategies to improve their loyalty. Drawing upon the theory of relationship marketing, a structural model is constructed to examine the impacts and mechanisms of personal media bloggers' attributes and communication on social presence, fanship, intention to use, and word of mouth. This research focuses on two dimensions of personal media bloggers' attributes: expertise and attractiveness. A sample of 155 highly active personal media users in China was collected through a questionnaire for analysis and validation. The findings reveal that expertise and communication have positive impacts on followers' intentions to continue following a blogger, while attractiveness has a significant, positive, and direct impact on word of mouth. Furthermore, this study shows that social presence and fanship play mediating roles in the effects of expertise and communication on followers' usage intentions and word of mouth. The research results provide valuable insights for personal media operators and marketers seeking to improve followers' loyalty and encourage potential users to become more loyal fans.
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Objective: To investigate the clinical efficacy of PHILOS plates in the treatment of Vancouver B1 periprosthetic femoral fracture (PFF) and to validate its biomechanical reliability via finite element analysis and mechanical testing on the Synbone femoral models. Methods: Ten males and eight females with Vancouver B1 PFF who underwent PHILOS plate fixation between September 2017 and January 2022 were selected. The average age was 72.61 ± 8.19 years, with a range of 57-86 years old. X-ray films were taken to assess the fracture healing situation around the femoral prosthesis as well as the position of the PHILOS plates and femoral prosthesis. Two different plates (the PHILOS plate and the Cable GTR plate) were used for fixation, and the differences in biomechanical stability of the two fixation methods were compared using finite element analysis and mechanical testing on the Synbone femoral models to validate the biomechanical dependability of the PHILOS plate. Results: All 18 cases were followed for at least 1 year, as a result. The average period of follow-up was 17 months, ranging from 12 to 36 months. At the most recent follow-up, Harris scores for the hip joints of patients ranged from 82 to 89, with an average score of 86. The X-rays revealed that all fractures surrounding the femoral prosthesis had healed and that there was no looseness in the femoral prosthesis. None of the PHILOS license plates had expired. All patients were able to perform full-load walking, and pain and claudication in affected limbs were significantly reduced. Finite element analysis and mechanical testing of the Synbone femoral model revealed that the fixation effect of the PHILOS group was superior to that of the Cable group; consequently, PHILOS plates can be used to effectively fix fractures around the proximal femoral prosthesis. Conclusion: PHILOS plates are initially used in the treatment of Vancouver B1 PFF, which may be a good choice due to their simpler operation, lower medical costs, and satisfactory clinical efficacy.
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Due to its rich nutritional value, yak milk is an important food source in the alpine pastoral areas. However, yaks have a low milk yield. The Hippo pathway participates in cell proliferation and organ development. We aimed to determine the regulatory mechanism of this pathway in yak mammary cells. A greater understanding of how the expression of its essential genes influence the reproductive cycle could lead to improvements in lactation performance. The expression levels of the key genes MST1, LATS1, YAP1, and TEAD1 were detected by quantitative real-time PCR, Western blotting, and immunohistochemistry during the growth, lactation, and dry periods (GP, LP and DP, respectively). The MST1 and LATS1 mRNA and protein expression level was highest during GP and lowest during LP. The YAP1 and TEAD1 mRNA and protein expression level decreased from GP to LP and DP. MST1 and LATS1 were expressed in the cytoplasm whereas YAP1 and TEAD1 were expressed in the nucleus and cytoplasm, respectively. The differential expression of MST1, LATS1, YAP1, and TEAD1 expression in the yak mammary gland during different developmental stages strongly suggests that they play an important role in the regulation of developmental functions under different physiological conditions.
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OBJECTIVE: Patients with adult growth hormone deficiency (AGHD) confer a heightened risk of cardiovascular disease and increased mortality because of metabolic disorders. Growth differentiation factor-15 (GDF-15) plays an important role in predicting metabolic abnormalities. We sought to investigate the correlation between GDF-15 and cardiovascular risk in AGHD patients. METHODS: The study enrolled 80 AGHD patients and 80 healthy subjects. We analyzed the association between GDF-15 and some major biochemical indicators. The potential association between GDF-15 and cardiovascular disease risk was analyzed. RESULTS: The AGHD group exhibited increased waist-hip ratio and high-sensitivity C-reactive protein (hs-CRP) and lipid levels compared with the healthy control group. Serum GDF-15 levels in AGHD group were elevated significantly compared with the control group (P < 0.001). GDF-15 levels were negatively associated with insulin-like growth factor-1 in AGHD group (P=0.006) and positively correlated with waist-to-hip ratio (P=0.018), triglycerides (P=0.007), and hs-CRP (P=0.046). In addition, GDF-15 was positively correlated with Framingham risk score significantly after adjustment for other factors (r = 0.497, P < 0.001). Moreover, GDF-15 was an independent risk factor for cardiovascular disease in AGHD patients after adjusting for traditional cardiovascular risk factors. CONCLUSION: Elevated GDF-15 levels were significantly associated with cardiovascular risk factors and can be considered as a predictive biomarker of cardiovascular risk in AGHD patients.
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Objective: Adult growth hormone deficiency (AGHD) is a rare chronic inflammatory disease caused by damage to the pituitary gland and is accompanied by disorders of multiple metabolic pathways. By examining the correlation between the serum mesencephalic astrocyte-derived neurotrophic factor (MANF) levels of AGHD patients and those of normal controls, we hope to elucidate the close relationship among MANF, lipid metabolism and insulin resistance in AGHD and discuss the potential therapeutic value of MANF. Methods: This study included 101 AGHD patients and 100 healthy subjects matched for sex, age, height, and weight. Anthropometric parameters and biochemical indicators such as body mass index, waist circumference, hip circumference, serum MANF level, blood lipids and insulin level were measured. The above patients were also divided into several subgroups for correlation analysis based on indicators such as insulin resistance and BMI. Results: The serum circulating MANF content of AGHD patients was significantly lower than that of the normal control group (5.235 (0.507-17.62) ng/ml (n=101) vs. 10.30 (1.84-16.65) ng/ml (n=100); p<0.0001), and circulating MANF levels were linearly correlated with HOMA-IR in the AGHD population (R=0.481, P=0.0041). When MANF was at pathological concentrations (lower than the mean circulating MANF of normal controls), the lowest concentration tertile (OR=21.429 p<0.0001) had a significantly higher disease odds ratio, Framingham risk score and 10-year risk of atherosclerotic cardiovascular disease than the highest concentration tertile. Conclusions: MANF has a significant correlation with insulin resistance in the AGHD state. There is a strong correlation with abnormal glucose and lipid metabolism in the obese AGHD population. MANF is also a good assessment factor for the risk of cardiovascular disease in AGHD patients and has excellent therapeutic potential.
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Biomarcadores/sangre , Enfermedades Cardiovasculares/diagnóstico , Trastornos del Crecimiento/complicaciones , Factores de Crecimiento Nervioso/sangre , Adulto , Anciano , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Adulto JovenRESUMEN
We present a new heteroditopic ligand (3pyCCMoid) that contains the typical skeleton of a curcuminoid (CCMoid) decorated with two 3-pyridyl groups. The coordination of 3pyCCMoid with ZnII centres results in a set of novel coordination polymers (CPs) that display different architectures and dimensionalities (from 1D to 3D). Our work analyses how synthetic methods and slight changes in the reaction conditions affect the formation of the final materials. Great efforts have been devoted toward understanding the coordination entities that provide high dimensional systems, with emphasis on the characterization of 2D materials, including analyses of different types of substrates, stability and exfoliation in water. Here, we foresee the great use of CCMoids in the field of CPs and emphasize 3pyCCMoid as a new-born linker.
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Osteoporosis is a severe bone disease characterized by a decrease in the density and structure of bones, with high risks of fractures. Pilose antler peptide (PAP), extracted and purified from deer antlers, can promote regeneration and fracture healing, and strengthen sinews and bone. To determine whether PAP can promote osteoblast development and to elucidate the molecular mechanisms underlying its functions, the present study investigated the effects of PAP on osteoblast proliferation, differentiation and mineralization, and the role of the insulin signaling pathway using MTT assay, alkaline phosphatase activity assay, western blot analysis and reverse transcription-quantitative PCR. The present results suggested that PAP promoted osteoblast proliferation, differentiation and mineralization in vitro via the insulin signaling pathway. The effect of PAP on insulin signaling in osteoblasts may be mediated via the ERK pathway and partially by the PI3K/Akt pathway. The present results indicated that PAP could potentially be developed as an alternative treatment strategy for bone diseases related to diabetes characterized by insulin signaling impairment.
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OBJECTIVE: The relationships between body fat distribution, the adipokine adipsin and metabolic risks were assessed in patients with adult growth hormone deficiency (AGHD) before and after growth hormone (GH) treatment. METHODS: Sixty newly diagnosed AGHD patients were included in our study, 24 of whom were evaluated after at least one year of GH treatment. Anthropometric parameters, glucolipid metabolism and the adipokine adipsin were measured. Visceral adipose tissue (VAT) and body composition were evaluated using a dual-energy X-ray-absorptiometry (DXA) scanner. RESULTS: At baseline, the higher VAT group had worse glucolipid metabolism parameters. Basal GH was negatively associated with VAT (r=-0.277, p = 0.045), while minimal correlations were found with fat mass depots, such as limbs and trunk fat (all p > 0.05). Adipsin was correlated with total body fat (r = 0.543, p < 0.001), VAT (r = 0.563, p < 0.001) and insulin resistance (r = 0.353, p = 0.006). The effect of GH administration on fat distribution was mainly reflected in the reduction in VAT. Partial improvements were found in lipid profiles, including increased high-density lipoprotein (HDL) and decreases in triglycerides (TGs) and lipoprotein(a), while glucose metabolism showed little change. The adipsin level also decreased significantly. The best predictors of VAT at baseline were trunk fat and IGF-I, and after treatment, VAT was predicted by decreased adipsin and an increase in lean mass. CONCLUSIONS: (1) VAT is an important metabolic risk factor for AGHD patients. (2) GH treatment decreased body fat predominantly in the visceral and central fat depots. (3) The lipid profiles partially improved after treatment, while glucose metabolism showed little change.
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Distribución de la Grasa Corporal/tendencias , Factor D del Complemento/metabolismo , Hormona de Crecimiento Humana/sangre , Hormona de Crecimiento Humana/deficiencia , Grasa Intraabdominal/metabolismo , Adulto , Anciano , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Hormona de Crecimiento Humana/administración & dosificación , Humanos , Grasa Intraabdominal/efectos de los fármacos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
Changes in the levels of serum oxidative stress indexes, gastrointestinal hormones and inflammatory factors in children with different severity of reflux esophagitis (RE) were detected. Sixty child patients diagnosed with gastroesophageal reflux disease (GERD) via gastroscopy were selected and divided into non-erosive reflux disease group (NERD group, n=12) and RE group (n=48) according to whether there was esophageal mucosal injury. In RE group, the patients were further divided into grade I RE group (n=15), grade II RE group (n=18) and grade III RE group (n=15) based on the severity of mucosal injury. None of the child patients took PPI and domperidone within 2 weeks before enrollment. The content of malondialdehyde (MDA) and total superoxide dismutase (T-SOD) in the esophageal mucosa was detected. The changes in the levels of serum vasoactive intestinal peptide (VIP), motilin, interleukin-1ß (IL-1ß), IL-8 and tumor necrosis factor-α (TNF-α) were determined. The DeMeester score was the highest in grade III RE group, followed by grade II RE group, grade I RE group and NERD group (P<0.05). The content of MDA in the esophageal mucosa was higher in RE group than that in NERD group, and the T-SOD activity declined with the increased severity of injury (P<0.05). In the three RE groups, the level of plasma VIP was significantly higher, while the motilin level was remarkably lower than those in NERD group (P<0.05). With the increased severity of disease, the expression levels of serum IL-1ß, IL-8 and TNF-α in RE group were gradually raised (P<0.05). RE patients have strong oxidative stress and inflammatory response, an increased level of serum VIP, a regulator of gastrointestinal motility, and a decreased level of motilin. Controlling the changes in the above factors using effective treatment means can improve the development of GERD.
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[This corrects the article DOI: 10.1039/C8RA08334G.].
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We have studied the single-molecule conductance of a family of curcuminoid molecules (CCMs) using the mechanically controlled break junction (MCBJ) technique. The CCMs under study contain methylthio (MeS-) as anchoring groups: MeS-CCM (1), the free-ligand organic molecule, and two coordination compounds, MeS-CCM-BF2 (2) and MeS-CCM-Cu (3), where ligand 1 coordinates to a boron center (BF2 group) and to a CuII moiety, respectively. We found that the three molecules present stable molecular junctions allowing detailed statistical analysis of their electronic properties. Compound 3 shows a slight increase in the conductance with respect to free ligand 1, whereas incorporation of BF2 (compound 2) promotes the presence of two conductance states in the measurements. Additional experiments with control molecules point out that this bistability is related to the combination of MeS- anchoring groups and the BF2 moiety within the structure of the molecules. Theoretical calculations show that this can be explained by the presence of two conformers once compound 2 is anchored between the gold electrodes. An energy minimum is found for a flat structure but there is a dramatic change in the magnitude and orientation of dipole moment (favouring a non-flat conformer in the presence of an external electric field) due to a conformational change of one of the terminal MeS- groups. The results thus point to an intricate interplay between the applied bias voltage and the molecule dipole moment which could be the basis for designing new molecules aiming at controlling their conformation in devices.
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The synthesis and characterization of a family of [60]fullerocurcuminoids obtained via Bingel reactions is reported. The new C60 derivatives include curcumin and curcuminoids with a variety of end groups. Preliminary biological experiments show the potential activity of the compound containing a curcumin addend, which exhibits moderate anti-HIV-1 and radical scavenger properties, but no anti-cancer activity. In addition, the new fullerocurcuminoids exhibit HOMO/LUMO energy levels that are reasonably matched with those of perovskites and when they were tested in perovskite solar cells (PSCs) as the electron transporting material (ETM), photoconversion efficiencies ranging from 14.04%-14.95% were obtained, whereas a value of 16.23% was obtained for [6,6]-phenyl-C61-butyric acid methyl ester (PC61BM) based devices.
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Japanese encephalitis virus (JEV) is a highly fatal pathogen to human beings. Toll-like receptor 7 (TLR7) plays a role as the first host defense against most single-stranded RNA flaviviruses. This study aims to investigate the role of TLR7 in inducing adaptive immune response in mice against JEV. In vitro and in vivo studies were conducted to examine the expression of toll-like receptors (TLRs) in mice. After JEV infection, physical parameters of mice (survival rate and body weight) were evaluated, and organs or cells were collected for further analysis. The expression of TLR7 was increased significantly as compare to other TLR molecules post-JEV infection. The expression of CD80, CD86, and CD273 on bone marrow-derived dendritic cells was increased significantly in TLR7-/- mice. Furthermore, viral load was also increased significantly in TLR7-/- mice as compare to C57BL/6 mice. But there was no significant difference among survival rate and body weight in TLR7-/- mice as compare to C57BL/6. Interestingly, we also found that TLR8 was upregulated in TLR7-/- mice. The study concluded that TLR8 was upregulated in TLR7-deficient mice, and it might play a compensatory role in the immune response in TLR7-/- mice.
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The monthly sampling data from June 2012 to May 2013 were used to study the composition and structure of the crustacean zooplankton community in the lakes and rivers of Suzhou Industrial Park. The variations in density and biomass of the crustacean zooplankton and their relationship with the environment factors were investigated. The results showed that a total of 42 species of crustacean zooplankton were found, including 24 species of cladocerans which belonged to 6 families and 12 genera, and 18 copepods which belonged to 7 families and 13 genera. The dominant species were Diaphanosoma brachyurum, Bosmina longirostris, Sinocalanus dorrii and Cyclops vicinus in all seasons of the year both in the rivers and the lakes. The density and biomass of the crustacean zooplankton in summer and autumn were higher than that in winter and spring, and there were two peaks in summer and autumn respectively both in the lakes and the rivers. The average density and biomass of cladocerans in the rivers were significantly higher than that in the lakes. There was no significant difference in the average density of Copepods between the rivers and the lakes, but the biomass in the rivers was higher than that in the lakes significantly. There were significant differences in dissolved oxygen, pH, Secchi depth, total dissolved solids, salinity, total phosphorus, total nitrogen and ammonium nitrogen between the lakes and the rivers. Redundancy analysis showed that the distribution of most of crustacean zooplankton was positively correlated with water temperature, the salinity, COD(Mn) and total phosphorus concentrations and only the distribution of the species belonging to genus Daphnia and Scapholeberis was positively correlated with O2 concentration, pH, and Secchi depth in both the rivers and the lakes in Suzhou Industrial Park.